Project Summary More than 50% of adults treated for diabetes, hypertension, or lipid disorders have suboptimal medication adherence, a prominent barrier to continued improvement in chronic disease care in the United States. Primary care providers (PCPs) often fail to identify medication nonadherence and/or have insufficient time and training to address underlying reasons for it. In this project, we propose a patient-centered and technology-driven strategy to identify patients with adherence issues and apply a team approach to help them achieve evidence- based personalized goals for glucose, blood pressure, or lipids. This intervention extends the use of a widely available clinical decision support (CDS) infrastructure to support a model of care that, for the first time outside of a fully integrated care environment, will integrate retail pharmacists within the primary care team. The intervention relies on a continuous health informatics loop to do the following: (a) identify high-risk patients with adherence problems at the point of care by expanding the capability of an electronic medical record (EMR)-linked CDS to capture pharmacy claims data and measure adherence; (b) establish and maintain an auto-populating up-to-date registry of patients identified for proactive pharmacist outreach at retail pharmacy locations; (c) implement a pharmacist outreach strategy based on an information-motivation-behavioral framework recommended by the World Health Organization with demonstrated ability to influence adherence across a variety of clinical applications; and (d) coordinate care and adherence information by incorporating pharmacist assessment and action plans into CDS at subsequent office encounters. The intervention was conceptualized and designed with extensive input from PCPs and in collaboration with pharmacy leaders to ensure efficient integration with existing clinic staff and workflows. We will test the effectiveness of this intervention using a cluster randomized controlled trial in 20 primary care clinics with approximately 50,000 adults with suboptimally controlled diabetes, hypertension, or lipid disorders. We will evaluate intervention impact on objective measures of adherence (proportion of days covered) and changes in hypertension control, glycemic control, and statin use. We will assess health care costs and long-term cost-effectiveness using microsimulation modeling, and in secondary analysis, assess intervention impact on primary nonadherence, 10-year cardiovascular risk, the care experience from the provider, patient, and key stakeholder perspectives, and on patient-reported medication adherence measures. This project builds upon previous National Institutes of Health funded research conducted by our team and (a) extends the capabilities of EMRs already used in the care of tens of millions of Americans, (b) electronically integrates pharmacists within the primary care team, (c) has the potential to significantly improve chronic disease care and translate massive investments in health information systems into tangible health benefits for large numbers of patients.